Continued studies have been carried out during the last decade to develop drugs which would significantly inhibit the development of inflammation and relieve pain and fever as well as the pain and fever associated with inflammation. While much of this effort has been carried out in the steroid field, there have been compounds developed which are non-steroidal.
In particular, there have been many compounds developed as analgesic and/or anti-inflammatory agents which are characteristically described because they are acidic in nature. One such group of compounds has been developed from an indenyl ring system which has a side chain consisting of an alkanoic acid or carboxylic acid derivative thereof such as an ester, amide or salt. The ring system may further be substituted, however, the acid side chain function is necessary for activity. While many of these compounds have been found to be effective, they have had the drawback of causing various side effects, in particular, gastric hemorrhage and ulceration.
We have unexpectedly found a series of compounds which has an indenyl ring system similar to those described above and have a high degree of pharmacological activity, however, they do not have this characteristic acidic side chain which has heretobefore been described as essentially associated with analgesic and anti-inflammatory properties.
We have unexpectedly found that when this alkanoic acid side chain or derivative of these molecules is replaced by an ethynyl moiety a group which is not a functional derivative of a carboxylic acid and which is chemically and physically unrelated, it unexpectedly results in compounds which have pronounced pharmacological properties and are unexpectedly useful for the relief and inhibition of inflammation conditions.
We have found that these ethynyl compounds are novel.
We have found that the compounds of this invention are effective in the treatment of inflammation and the control of arthritic conditions associated with inflammation without causing serious side effects.
We have further found that the compounds of this invention possess useful analgesic and antipyretic properties and are useful in the treatment of pain and/or fever without causing serious side effects.
We have further unexpectedly found that the compounds of this invention are pharmacologically effective with diminished gastric hemorrhage or ulceration as is commonly associated with those agents having the acidic side chain moiety present.
We have also found an entirely novel class of pharmaceutical compositions which contain the compounds of this invention as active ingredients.
We have still further found a novel process for the synthesizing of these compounds.